Cytochrome P-450 dependent monooxygenases model system: Rapid and efficient oxidation of primary aromatic amines to azo derivatives with sodium periodate catalyzed by manganese(III) Schiff base complexes

Article abstract of DOI:10.1016/j.bmc.2004.06.029

Rapid and efficient oxidation of primary aromatic amines was investigated. Mn(III)-salophen catalyst can catalyze the oxidation of primary aromatic amines to azo derivatives with sodium periodate. The ability of various Schiff base complexes in this oxidation system was also investigated.

Full text of DOI:10.1016/j.bmc.2004.06.029

Bioorganic & Medicinal Chemistry 12 (2004) 4673–4677
Cytochrome P-450 dependent monooxygenases model system:
rapid and efficient oxidation of primary aromatic amines to
azo derivatives with sodium periodate catalyzed by
manganese(III) Schiff base complexes
a,
Valiollah Mirkhani, Shahram Tangestaninejad, Majid Moghadam and
a
b
*
a
Maryam Moghbel
a
Department of Chemistry, Isfahan University, Isfahan 81746-73441, Iran
b
Department of Chemistry, Yasouj University, Yasouj 75914-353, Iran
Received 20 April 2004;revised 15 June 2004;accepted 22 June 2004
Available online 24 July 2004
Abstract—Rapid and efficient oxidation of primary aromatic amines was investigated. Mn(III)-salophen catalyst can catalyze the
oxidation of primary aromatic amines to azo derivatives with sodium periodate. The ability of various Schiff base complexes in this
oxidation system was also investigated.
Ó 2004 Elsevier Ltd. All rights reserved.
1
. Introduction
ists as model compounds for the active site of
cytochrome P-450, since they have features in common
with metalloporphyrins with respect to their electronic
structure and catalytic activity. The electronic and steric
nature of the metal complex can be tuned by introducing
electron-withdrawing and electron-releasing substituents
and bulky groups in the ligand. Manganese, chromium,
nickel, and cobalt Schiff base complexes have been used
Oxidation is one of the most important reactions for the
metabolism of biotic substrates and many enzymes are
known to catalyze various types of oxidation. Amongst
such oxidizing enzymes, the heme-containing mono-
oxygenase cytochrome P-450 has been most extensively
1
studied. Many metalloporphyrin complexes have been
1
4–23
synthesized to reproduce the function of cytochrome
P-450 and some well-designed iron(III) and manga-
nese(III) porphyrins have been found to be efficient cat-
as catalysts for oxidation reactions.
Previously, we have reported the use of Mn(III)-salo-
phen complexes in the alkene epoxidation and oxidative
2
alysts for O- and N-dealkylation, olefine and arene
5
3
,4
24,25
epoxidation,
6
alkane hydroxylation, and oxidation
of nitroso and primary aromatic amines to nitro deriv-
decarboxylation of carboxylic acids.
In continua-
26,27
tion of our research in the oxidation of amines,
here we report the rapid and efficient oxidation of pri-
mary aromatic amines to azo derivatives with sodium
periodate catalyzed by manganese(III) salophen com-
plex.
7
atives. Various single oxygen-atom donors such as iod-
osylbenzene, hypochlorites, potassium monopersulfate,
and periodates have been used for this transforma-
8
–13
tions.
On the other hand, metal complexes of salen and salo-
phen ligands also aroused the interest of synthetic chem-
This catalytic system exhibits a high activity in the oxi-
dation of primary aromatic amines with sodium perio-
date in 1:1 CH CN/H O mixture in the presence of
3
2
imidazole as axial ligand (Scheme 1).
Keywords: Schiff base complexes;Primary aromatic amines;Periodate.
*
Corresponding author. Tel.: +98-311-7932713;fax: +98-311-
689732;e-mail: mirkhani@sci.ui.ac.ir
The type of metal ion and Schiff base and the nature of
reactive intermediate were also investigated.
6
0
968-0896/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmc.2004.06.029

4674
V. Mirkhani et al. / Bioorg. Med. Chem. 12 (2004) 4673–4677
Mn(III)-Salophen/NaIO4
NH2
N N
Imidazole/ CH CN/H O, RT
3
2
R
R
R
Scheme 1.
2
. Results and discussion
Table 1. Oxidation p-toluidine by various metal Schiff base complexes
with sodium periodate
a
a
a
2.1. Oxidation of primary aromatic amines with different
metal Schiff base complexes
Schiff base
Yield (%)
after 10min
Yield (%)
after 20min
Yield (%)
after 30min
1
2
3
4
5
6
7
8
9
95
33
8
96
35
8
98
38
8
In a preliminary approach to the periodate anion activa-
tion by metal Schiff base complexes, we investigated the
activity of various Schiff base complexes of Fe, Mn, Co,
and Ni as metal ions. The obtained results on catalytic
oxidation of p-toluidine with sodium periodate in the
presence of different Schiff base complexes (Fig. 1) sum-
marized in Table 1. The results indicated that the nature
of the metal ion has an important role on the catalytic
activity of Schiff base complexes. The iron, cobalt, and
nickel complexes give small amount of the correspond-
ing azo compound in the oxidation of p-toluidine. How-
ever, the use of manganese(III) complexes give higher
oxidation product in the oxidation of p-toluidine.
8
9
9
7
8
8
14
8
16
10
31
8
17
13
34
9
29
8
1
1
0
1
16
9
19
9
23
11
a
GC yields.
Table 2. Effect of solvent on oxidation of p-toluidine with Mn(salo-
phen)/NaIO
4
system
In comparing the influence of Schiff base ligands on
calatytic activity, the hindered Schiff base ligand,
a
a
Solvent
Yield (%)
after 5min
Yield (%)
after 10min
salophen, exhibits
a
significant greater catalytic
CH
CH
CH
CH
3
3
3
3
CN/H
COCH
OH/H
CH OH/H
/H
CCl /H O
2
O
85
42
17
25
3
95
57
27
32
3
power than the unhindered Schiff base ligand, salen.
The similar situation have been observed with metallo-
3
2
/H O
2
O
2
8
porphyrin complexes and NaOCl as oxygen donors.
2
2
O
CHCl
3
2
O
Other oxygen-donors such as KHSO , NaOCl, and
5
4
2
3
3
H O were examined for oxidation of primary aromatic
2
2
a
GC yields.
amines under various reaction conditions, but higher
activity was observed with sodium periodate than with
the other oxygen donors.
2
.2. Effect of solvent on the oxidation of p-toluidine
Among the 1:1 mixture of methanol, ethanol, acetone,
acetonitrile (single phase systems), chloroform, and car-
bontetrachloride (two phase systems with Bu NBr as
phase transfer catalyst) with water, the 1:1 acetonitrile/
water mixture was chosen as the reaction medium, be-
cause metal Schiff base complexes are highly soluble in
this solvent and higher azo yields were observed. The re-
sults were shown in Table 2.
Y
4
X
O
N
O
N
X
N
N
Y
N
N
M
M
z
z
M
z
X
Y
1
2
3
4
5
6
7
8
9
Mn
Mn
Fe
C
C
C
C
C
6
H
H
H
H
H
4
4
4
4
4
)
)
H
NO
H
Cl
Cl
Cl
-
2
.3. Effect of axial ligand on the oxidation of p-toluidine
6
6
6
6
2
One important aspect of this catalytic system is the mod-
ification of the oxidation rate by addition of small
amount of imidazole to the reaction mixture. The for-
mation of azobenzene in the absence of axial ligand is
very slow and the yields are always below 10%, whereas
the amount of azobenzene reaches to 98% in the cata-
lyzed reaction with the imidazole as the axial base.
Co
Ni
H
H
-
Mn
Fe
(CH
(CH
2
2
2
H
Cl
Cl
Cl
Cl
Cl
Cl
2
H
Mn
Fe
C
C
6
6
H
H
4
4
)
)
H
H
The effect of different axial ligands upon the oxidation
rate decreased in the order: imidazole=1-methylimidaz-
ole>4-t-buthylpyridine>4-methylpyridine>2-methyl-
pyridine>pyridine.
1
0
Mn
Fe
(CH
2
2
2
2
H
11
(CH
H
Figure 1. Transition metal Schiff base complexes used in this study.

V. Mirkhani et al. / Bioorg. Med. Chem. 12 (2004) 4673–4677
4675
2
7
2.4. Oxidation of primary aromatic amines with sodium
periodate catalyzed by Mn(III)-salophen
in the case of heterogeneous metalloporphyrin system
the yields are similar whereas the reaction times are
shorter.
The imidazole-modified Mn-salophen/NaIO oxidizing
4
system can be applied to oxidize a large number of pri-
mary aromatic amines in high to good yields at short
times and room temperature. All experiments were car-
ried out with 2equiv of sodium periodate per 1equiv of
amine. As shown in Table 3, the yields are between 57%
and 88% (isolated yields) and the product was azo deriv-
ative.
In the absence of manganese(III)-salophen catalyst,
NaIO has poor ability to oxidize primary aromatic
amines at room temperature (4–10% yields).
4
At present, it is obscure to us to indicate the mechanism,
but H NMR, IR, and mass spectrometry confirmed the
product.
1
Comparison of this homogeneous oxidizing system with
previously reported homogeneous metalloporphyrin
systems showed that in the Mn-salophen/NaIO sys-
4
2.5. Oxo manganese(V) species as the reactive interme-
diate
2
6
tem the yields are higher than that metalloporphyrin/
NaIO systems and the reaction times are shorter, and
Although we have assumed the active manganese spe-
cies to be reactive (salophen)Mn(V) oxo intermediate,
4
4
Table 3. Oxidation of primary aromatic amines to azo derivatives with NaIO catalyzed by Mn(III)-salophen in the presence of imidazole
a
Yield (%)
Row
Substrate
Products
Time (min)
1
NH2
10
82
N
N
2
3
H C
NH2
H C
N
N
10
10
88
83
CH3
3
3
NH2
CH3
N
N
CH3 H C
3
4
5
C H
NH2
C H
N
N
C H
5
10
10
88
85
2
5
2
5
2
CH O
NH2
CH O
N
N
CH O
3
3
3
NH2
N
N
N
6
10
83
MeO
MeO
OMe
NH2
N
7
8
9
10
30
82
65
OMe
OMe MeO
NH2
N
N
Cl
Cl
Cl
NH2
N
N
30
30
69
61
CN
CN
NC
N
1
1
0
1
Br
NH2
Br
N
Br
NH2
N N
30
57
a
Isolated yields based on starting aromatic amine.

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V. Mirkhani et al. / Bioorg. Med. Chem. 12 (2004) 4673–4677
purified by silica gel plate or silica gel column (eluent:
CCl –Et O). The identities of products were confirmed
by IR and H NMR spectral data.
4
2
1
4. Conclusions
Although many oxidation systems that mimic cyto-
chrome P-450 dependent monooxygenase have been re-
ported, Mn(III)-salophen/NaIO catalytic system have
4
the following advantages: (i) short reaction time;(ii)
high efficiency for the oxidation of amines;(iii) ease of
preparation of the catalyst.
Figure 2. Absorption spectra of [Mn(III)-salophen]Cl in CH
The dashed curve is the same solution immediately after reaction with
excess NaIO
3 2
CN/H O.
4
.
In comparison with other reported Schiff-base oxidation
systems, performance of the novel Mn(III)-salophen/
NaIO system can be described as outstanding. There-
fore, in the list of suitable oxidants able to behave like
single oxygen donor to Schiff base complex, sodium per-
iodate is among the most efficient.
V
[
(salophen)Mn @O], by comparing the present spectral
28
observation with the previous reports, we could not
isolate this active species. It is pertinent to point out that
to date no (salophen)Mn(V) oxo species have yielded to
structural characterization, although Groves et al. and
others have characterize oxo manganese(V) porphyrin
4
2
9
complexes in recent years.
Acknowledgements
When a clear brown solution of Mn(III)-salophen in
acetonitrile is treated with sodium periodate, it immedi-
ately turns dark. The appearance of a new absorption
band (with kmax =520–530nm, Fig. 2) is strongly remi-
niscent of the spectral change obtained during the
conversion of the Mn(III)-salophen cation to the corre-
sponding oxo manganese(V) species. Upon standing, the
dark brown solution fades to the original light brown
within 10min. When the same experiment is carried
out in the presence of p-toluidine, the dark brown
solution immediately changed to its original light brown
color.
The partial support of this work by Isfahan University
Council of Research is acknowledged.
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